Safety of Erythropoietin and Melatonin for Very Preterm Infants With Intraventricular Hemorrhage

Summary

Very preterm infants are prone to numerous medical complications with lifelong impact. Amongst the most serious are significant intraventricular hemorrhage (sIVH) and the subsequent progression to posthemorrhagic hydrocephalus (PHH). Currently, the only treatment for PHH is surgery, most commonly with shunts that are prone to malfunction across the lifespan. Preclinical data show that melatonin (MLT) and erythropoietin (EPO), when administered in a sustained dosing regimen, can prevent the hallmarks of progression from early postnatal sIVH to subsequent PHH. The investigators will perform a Phase I, single institution, randomized, double-blind trial for very preterm infants with sIVH to define a safe combination dose of MLT and EPO. A maximum of 60 very preterm neonates with sIVH will be enrolled, treated through 33w6/7d, and followed to 37w6/7d. Neonates will be randomized 3:1 between MLT+EPO and placebo, with all receiving standard of care. The primary endpoint is a composite serious adverse event (SAE)/dose limiting toxicity (DLT). The investigators hypothesize that the MLT+EPO SAE/DLT rate will not be higher than the placebo rate. Secondary outcomes will be rate of co-morbidities of preterm birth. Exploratory data, collected to guide design of future clinical trials for efficacy, will include serial neuro-imaging metrics acquired from clinical images, serial neonatal neurodevelopmental examinations, serum and urine MLT and EPO levels, and liquid biomarkers. Successful implementation of this initial safety trial will provide essential data to guide the next stage of clinical trials to test if sustained MLT+EPO treatment can reduce the need for surgical intervention, and avoid the lifelong burden of shunted hydrocephalus.

Conditions

• Intraventricular Hemorrhage of Prematurity

Interventions

COMBINATION_PRODUCT

MLT+EPO

Melatonin component will be a daily dose of 30 mg/kg enteral administered in the evening in a split dose given at cares/feedings. EPO component is a two-stage regimen with high dose EPO (1000 U/kg/dose q 48 hrs ± 2hr subcutaneously or intravenously) for 10 doses followed by maintenance dose EPO (400 U/kg/dose q Monday, Wednesday, Friday subcutaneously or intravenously) to 33-6/7wk. Maintenance EPO dosing will begin on the day closest to completing the high dose series.

OTHER

Placebo

Placebo enteral and IV

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  collaborator NIH

• Johns Hopkins University

  lead OTHER

Principal Investigators

• Shenandoah Robinson, MD · Johns Hopkins University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

12 Hours

Max Age

2 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-04-30

Primary Completion

2027-09-30

Completion

2027-09-30

FDA Drug

Yes

Countries

• United States

Study Locations